| Autor: |
Shanye Yin, Susan Klaeger, Vipheaviny A. Chea, Isabel P. Carulli, Suzanna Rachimi, Katharine E. Black, Michael Filbin, Lida P. Hariri, Rachel S. Knipe, Robert F. Padera, Jonathan D. Stevens, William J. Lane, Steven A. Carr, Catherine J. Wu, Edy Yong Kim, Derin B. Keskin |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2023.1269335 |
| Popis: |
IntroductionSevere respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host’s response to SARS-CoV-2.MethodsTo gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.ResultsWe found signals of tissue injury and regeneration in lung fibroblast and alveolar type I/II cells, resulting in the production of highly immunogenic self-antigens within the lungs of COVID-19 patients. We also identified immune activation of the M2c macrophage as the primary source of HLA-I presentation and immunogenicity in this context. Additionally, we identified 28 lung signatures that can serve as early plasma markers for predicting infection and severe COVID-19 disease. These protein signatures were predominantly expressed in macrophages and epithelial cells and were associated with complement and coagulation cascades.DiscussionOur findings emphasize the significant role of macrophage-mediated immunity in the development of severe lung disease in COVID-19 patients. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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